Moving Beyond BCG in Bladder Cancer

Robert L. Ferris, MD, PhD

Lineberger Distinguished Professor

Executive Director

UNC Lineberger

Comprehensive Cancer Center and Chief of Oncology Services

UNC Health System

Chapel Hill, NC

AS MANY INITIATIVES are launched at the beginning of the new year, anticipating developments in different cancer types is a fun exercise. Given different scientific and clinical meeting schedules, such as the recent Society of Urologic Oncology (SUO) meeting, considering advances in genitourinary oncology in novel therapies is relevant.

BCG, one of the earliest innate immunotherapies used in bladder cancer, has given way to adaptive immunotherapies using immune checkpoint inhibitors. In an era of neoadjuvant immunotherapy, the role of cystectomy for immunotherapy-responsive and nonresponsive carcinoma in situ or invasive disease still plays a role, especially in expanding the survival advantage in these patients.

Additional approaches beyond those for localized early- or late-stage disease addressed during the SUO meeting in December in Dallas, Texas, include recent advances in the recurrent and metastatic setting, where antibody-drug conjugate strategies are undergoing evaluation. In addition, the role of theranostics and radiopharmaceuticals, such as lutetium Lu 177 vipivotide tetraxetan (Pluvicto), has grown dramatically in the past 2 years, as this column has noted.

The development of novel targets as well as unique payloads, including radioisotopes, provides interesting new agents to integrate into the typical endoscopic and open surgical procedures to document pathologic activity and response. This approach may eventually reduce the rates of recurrence and metastatic disease currently being targeted with systemic therapies. It could potentially provide perioperative strategies that, if imaging and other response surrogates can be developed, may reduce organ-disrupting surgery as we have seen in other preoperative, neoadjuvant, short-window, therapeutic treatments.

When the neurologic oncologic surgeon must interface with the medical and radiation oncologists, continuing multidisciplinary collaborations are required, which, although benefiting the patient, may increase costs and lead to some inconvenience. These may be outweighed by the reduced surgical extent and be offset by the patient’s return to the workforce with less health care required after cystectomy, or extended hospital admissions. In all, we expect 2025 to parallel recent years when therapeutic advances and the reordering of the sequence of therapies may continue; we await these exciting results.